Multivariable Mendelian Randomization and Mediation.

By E. Sanderson. Cold Spring Harbor Perspectives in Medicine, 2020

712 citations recorded by the source corpus.

Mendelian randomization (MR) is the use of genetic variants associated with an exposure to estimate the causal effect of that exposure on an outcome. Mediation analysis is the method of decomposing the effects of an exposure on an outcome, which act directly, and those that act via mediating variables. These effects are decomposed through the use of multivariable analysis to estimate the causal effects between three types of variables: exposures, mediators, and an outcome. Multivariable MR (MVMR) is a recent extension to MR that uses genetic variants associated with multiple, potentially related exposures to estimate the effect of each exposure on a single outcome. MVMR allows for equivalent analysis to mediation within the MR framework and therefore can also be used to estimate mediation effects. This approach retains the benefits of using genetic instruments for causal inference, such as avoiding bias due to confounding, while allowing for estimation of the different effects required for mediation analysis. This review explains MVMR, what is estimated when one exposure is a mediator of another in an MVMR estimation, and how MR and MVMR can therefore be used to estimate mediated effects. This review then goes on to consider the advantages and limitations of using MR and MVMR to conduct mediation analysis.

Subfields: Epidemiology, Genetics

View Paper: https://www.semanticscholar.org/paper/52397e5a1332f8a72b0f4de8d04f32a4859a5cc5

How researchers see this paper

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In Epidemiology

1. E. Sanderson
2. George Davey Smith
3. N. Davies
4. R. Richmond
5. L. Howe
6. Amy E Taylor
7. J. Heron
8. G. Hammerton

In Genetics

1. E. Sanderson
2. N. Davies
3. George Davey Smith
4. R. Richmond
5. Amy E Taylor
6. L. Howe
7. J. Heron
8. G. Hammerton

Citations in the corpus

• Mendelian randomisation for mediation analysis: current methods and challenges for implementation (2019, methodology): “Two differing MR approaches can then be used which broadly mirror traditional non-IV regression-based approaches to mediation to decompose the direct and indirect effects: multivariable MR (MVMR) [19, 20] and two-step MR [21–23].”
• Mendelian randomization for cardiovascular diseases: principles and applications (2023, neutral): “35 As an example, multivariable MR analysis has been conducted to unravel which one (or more) of the atherogenic lipid-related traits accounts for the causal association with major CVDs.”